None listed
Conditions
Brief summary
This study will assess the anti-cancer activity of sulfasalazine in patients with advanced or metastatic pancreatic ductal adenocarcinoma. Who is it for? You may be eligible for this study if you are participating in the Cancer Molecular Screening and Therapeutics (MoST) Program (ACTRN12616000908437) and have SLC7A11-positive pancreatic ductal adenocarcinoma that has progressed following therapy with current standard of care. Study details All participants will be treated with oral sulfasalazine. It is usual to start taking sulfasalazine at a lower dose and gradually increase. Participants will start treatment by taking one 500mg tablet, three times a day. If the sulfasalazine is tolerated, the dose will be increased during the first cycle of treatment up to a maximum dose of four 500mg tablets, three times a day. To prevent low levels of folic acid that can occur with sulfasalazine treatment, participants will also take 1mg of oral folic acid tablets daily. Participants will be regularly assessed throughout the study in order to monitor safety and tumour response. Participants will have weekly clinic visits during Cycle 1 dose escalation. The frequency of visits declines to monthly later in the study. It is hoped that this study will help increase treatment options for patients with advanced pancreatic cancer.
Interventions
Participants will be commenced on treatment with sulfasalazine (500mg oral tablets) at 1.5 g per day in three evenly divided doses. The dose will be incrementally increased to the target dose (4.5 g per day in three evenly divided doses), subject to tolerability. The dose may be further escalated to 6 g per day, in three evenly divided doses, subject to no significant intolerance and study PI approval.
Participant acetylator status, which affects how quickly sulfasalazine is processed in the bo
Participants will be commenced on treatment with sulfasalazine (500mg oral tablets) at 1.5 g per day in three evenly divided doses. The dose will be incrementally increased to the target dose (4.5 g per day in three evenly divided doses), subject to tolerability. The dose may be further escalated to 6 g per day, in three evenly divided doses, subject to no significant intolerance and study PI approval. Participant acetylator status, which affects how quickly sulfasalazine is processed in the body, is used to inform the dose escalation schedule during the first treatment cycle. For fast acetylators, the sulfasalazine dose is expected to increase to 3g per day on Day 4, further escalated to the target dose on Day 8 and may be further escalated to 6g per day on Day 15 subject to tolerability and PI approval. For slow acetylators, the dose is expected to increase to 3g per day on Day 8, further escalated to the target dose on Day 15 and may be further escalated to 6g per day on Day 22 subject to tolerability and PI approval. All participants will continue the study treatment until clinical or radiological progression or until treatment discontinuation criteria are met. Tablet counts will be performed by the study team to assess adherence. To prevent low levels of folic acid that can occur with sulfasalazine treatment, participants will also take 1mg of oral folic acid tablets daily.
Sponsors
Australian Genomic Cancer Medicine Centre Ltd t/a Omico
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged >=18 years old. 2. Histologically or cytologically confirmed locally advanced (Stage III) unresectable or metastatic (Stage IV) PDAC. 3. Adequate archival tissue for comprehensive genomic profiling. 4. Disease must have progressed after one-line of standard fluoropyrimidine- or gemcitabine-based chemotherapy for advanced disease. Treatment break within the upfront chemotherapy regimen is considered the same line of therapy and is permitted. 5. Have had one-line of systemic therapy for advanced disease. Patients who have had two lines of systemic therapy or are intolerant of second-line treatment may be eligible after consultation with the study Chief Investigators. 6. ECOG performance status score of 0-1. 7. Life expectancy >12 weeks. 8. Measurable disease as defined by RECIST version 1.1. 9. Presence of tumour amenable to a second biopsy. 10. Adequate haematological indices as defined by: a. Absolute neutrophil count >=1.0 x 10^9/L b. Haemoglobin >=100 g/L c. Platelet count >=100 x 10^9/L d. Bilirubin <1.5x ULN e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <1.5x ULN; or <5.0x ULN if liver metastases are present f. International normalised ratio (INR) <1.3 in the absence of anticoagulation therapy. 11. Adequate renal function, as defined by Creatinine Clearance (CrCl) >=50mL/min using Cockcroft formula. 12. Women of childbearing potential and men must use effective contraception during the study and for at least 90 days after the last dose of study medication. Women of childbearing potential must have a negative screening serum pregnancy test. 13. Ability to adhere to the study visit schedule and understand and comply with all protocol requirements and instructions from study staff. 14. Provision of written informed consent.
Exclusion criteria
1. Diagnosis of other histology types other than ductal adenocarcinoma, including but not limited to pancreatic acinar cell carcinoma, well-differentiated neuroendocrine tumour, neuroendocrine carcinoma, or lymphoma. Mixed histology with predominantly adenocarcinoma component is eligible. 2. Uncontrolled diabetes, defined as HbA1c >10% in previous 3 weeks. 3. Pregnant or breastfeeding. 4. Major surgery within 28 days prior to Day 1. Biliary stent placement or endoscopic procedure is permitted. 5. Radiation therapy within 28 days prior to Day 1. 6. Uncontrolled central nervous system or brain metastases. 7. Uncontrolled hypertension (systolic blood pressure [SBP] >180mmHg or diastolic blood pressure [DBP] >105mmHg). 8. New York Heart Association Class III or IV congestive heart failure. 9. Current clinical or laboratory evidence of active or uncontrolled infection. 10. History of uncontrolled severe asthma or atopic dermatitis requiring hospitalization. 11. Concomitant advanced solid or haematological malignancy with an expected prognosis that is worse than the index pancreatic adenocarcinoma. 12. Active major gastrointestinal bleeding. 13. Known hypersensitivity or allergic reactions to salicylates or sulphonamide derivatives, including antibacterial sulphonamides, oral hypoglycaemics and thiazides. 14. Known intestinal or urinary obstruction or porphyria. 15. Participation in studies of investigational products within 28 days prior to Day 1, or 5 half-lives, whichever is longer. 16. Clinically significant and uncontrolled medical condition considered a high risk for participation in an investigational study or a likelihood that the potential participant will be unable to comply with protocol requirements and complete the trial (e.g. emphysema requiring supplemental oxygen, poorly controlled arrhythmia, psychiatric illness, Alzheimer's disease). 17. Current abuse of alcohol or drugs.
Outcome results
None listed